The immediate objectives of the program are to synthesize and characterize new pharmacological tools for the study of excitatory amino acid transmitter systems in the brain, to use these new agents (and preexisting substances) to advance knowledge of central excitatory amino acid transmitter systems, and to design and synthesize new drugs with defined actions on these transmitter systems for the treatment of neurological and/or psychiatric disorders. New excitatory amino acid agonists and antagonists will be synthesized and their actions characterized by well-proven screening techniques including electrophysiological testing in vitro (isolated rat spinal cord and hippocampal slices) and in vivo (cat spinal cord and brain) as well as radioligand binding techniques on rat brain membranes. Drug potential will be assessed in a number of collaborative ventures and will include tests on mice and rats for anticonvulsant, muscle relaxant and anxiolytic properties, and the ability of the substances to prevent ischemic and other types of neuronal degeneration. Associated projects will include the synthesis of potential uptake blockers of excitatory amino acids, new agents for the preparation of affinity chromatography ligands, the biosynthesis of sulfur-contain% amino acids, and the chemical and pharmacological characterization of a brain fraction with pronounced neuro-depressant activity.